| Project/Area Number |
22K06792
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48010:Anatomy-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
イスラム エムディノビウル 山口大学, 大学院医学系研究科, 講師 (80759671)
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| Co-Investigator(Kenkyū-buntansha) |
篠田 晃 山口大学, 大学院医学系研究科, 教授 (40192108)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2024: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | HAP1 / Neuroprotection / ChAT / Huntingtin / STB / Stigmoid body / Motor neuron / Autonomic neuron / Motoneuron / Neurodegeneration |
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| Outline of Research at the Start |
Stigmoid body (STB)/huntingtin-associated protein 1 (HAP1) can protect neurodegenerative apoptosis in vitro. In this study, we will examine the changes of autonomic neurons and their functions using our recently generated HAP1-KO mice, and will elucidate the differences in motor function behavior test battery between aged-wild-type mice and aged-motor-neuron-specific HAP1-TG mice that we genetically engineered. The outcomes of this study may shed light on yet-to-be-uncovered new diagnostic or therapeutic applications for certain neurodegenerative diseases.
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| Outline of Annual Research Achievements |
In the first year, we clarified the relationships of STB/HAP1 with ChAT in the brainstem, particularly in motoneurons and autonomic neurons. In the second year, we further investigated the relationships of STB/HAP1 with ChAT in the forebrain. We found that the cholinergic neurons of MS, VDB, and LS that are mainly projected to the hippocampus and parahippocampal gyrus might be protected by STB/HAP1 to regulate the sensory-motor integration or cognition during neurodegenerative/psychotic stresses. In contrast, the STB/HAP1 and ChAT co-expression devoid area (e.g., CPU and cortex) might be more prone to neurodegeneration. In addition, we also clarified that HAP1 is highly expressed in the submucosal plexuses of the enteric nervous system and the lingual Ganglia.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We have completed objectives 1 and 2 of our current research, and the other objectives are progressing smoothly. We have presented our research findings at various regional, national, and international conferences. We have also published two articles in peer-reviewed international journals.
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| Strategy for Future Research Activity |
1. We will clarify the immunohistochemical relationships of STB/HAP1 with the Huntingtin in the brain and spinal cord.
2. We will clarify the immunohistochemical relationships of STB/HAP1 with the Serotonin in the brain.
3. We will examine STB/HAP1-expression in autonomic ganglion and determine the autonomic neuron number changes in the CNS/PNS of HAP1-KO mice. Furthermore, we will compare autonomic function-related behavioral test batteries between wild-type and HAP1-KO mice.
4. The aged mouse is an excellent model for examining motor neuron degeneration vulnerability. We will also determine the changes in motor neuron number and motor function-related behavioral test battery comparison between aged-wild type and aged-HAP1-TG mice.
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